About this Author

College chemistry, 1983

The 2002 Model

After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe

December 20, 2005

Does Celebrex Have A Future At All?

Posted by Derek

I have a correspondent who's written me a few times about the Vioxx/Celebrex/NEJM situation, and I thought I'd pass along some of his thoughts. He's not buying my idea that the New England Journal is worried about being sued, for one thing. As he points out, the various liability battles that have taken place over the last twenty years also have had potential for that sort of thing, and no one's done it yet.

And as for Pfizer's big Celebrex trial, he regards it as four years worth of lawsuit insurance, and cheap at the price. That's a reasonable idea, unfortunately, but I wonder if that would slow down a sufficiently motivated member of the plaintiff's bar. After all, they could make the argument that the company clearly had no idea (italics theirs!) if their product posed a cardiovascular risk or not - that's why they had to run a trial, naturally - and meanwhile had recklessly exposed consumers to the dangers of this insufficiently tested drug. . .man, once you start on those italics, it's hard to stop.

However, my correspondent isn't even sure that this is an ethical trial at all. (That Forbes article I linked to the other day had quotes from others raising such concerns). If you believe that COX-2 inhibitors have mechanism-based cardiac risks (a hypothesis publicized best by Garrett Fitzgerald at Penn), then Celebrex isn't going to be able to escape. There's room to argue that the COX-2 drugs don't have as good a gastrointestinal safety profile as had been hoped, either, which would take away another reason for their existence (and another ethical rationale for the new trial). Celebrex had better be good at relieving pain. . .

I should point out that if these effects are real, neither of them are things that would have been obvious earlier in the development of the COX-2 drugs. The rationales for their development were actually quite compelling at the time (just ask the University of Rochester - anyone heard from them recently?) But that's drug development for you. Every single new drug has risks, many of which aren't even known until millions of people take them. Would that it were different, but it isn't.

Hey, did the FDA not review all the data current to Jan 2005 (probably more like Nov or Dec 2004) and conclude that Vioxx had the most serious risk, Bextra a somewhat less risk, and Celebrex a minimal risk?

Hello I am on celebrex and have been for sometime my dosage is 2-200mg in the morning and 1-200mg at bedtime. Am I more at a risk for taking a bigger dose than just taking 1 per day ? Thanks , Sarge Madden

I have been on Celebrex for several years and also have a Master's in biochemistry. After all the media hype hit the airwaves, I did considerable digging within the medical, I emphasize MEDICAL literature. I found that there are over 40 controlled trials looking at Celebrex that have found no link whatsoever between Celebrex use and increased cardiovascular risk. It's the one trial that paints Celebrex in a negative light that gets all the attention from the laypress. Of course, no one hears about the fact that if aspirin or acetaminophen (Tylenol) were to be reviewed for approval by the FDA today that they would not have a chance in hell of gaining approval. Currently there are over 40,000 cases of Tylenol overdose per year. There are also 16,500 deaths due to gastrointestinal bleeds caused by nonsteroidal anti-inflammatories per year. The average ambulance ride costs $8K, a blood transfusion costs $40K. Personally, I'll fork over the dough for my Celebrex as insurance against the latter two options. Currently, Celebrex is the only anti-inflammatory drug on the market that can be taken along with aspirin (all traditional non-steroidals compete with aspirin for the same binding site on blood platelets, Celebrex does not). In fact, in a clinical trial of over 22,000 doctors (sponsored by the National Institute of Health, not Pfizer) showed that anyone who took aspirin and traditional NSAIDs together for over 60 days completely negated the beneficial effects of aspirin on blood platelets. A couple more interesting tidbits: in a study sponsored by the FDA and Kaiser Permanente, Celebrex was actually 14% less risky than the control (anyone who had not used NSAIDs in 60 or more days) in causing heart attack or sudden cardiac death. Vioxx over 25mg increased risk of acute MI or sudden cardiac death by 300% over the control. COX2 class effect? I think not. In another study of the same design in California's state medicaid population, similar results were repeated. Pfizer's Bextra was on the market when this database was analyzed and actually showed less risk than no NSAIDs for 60 or more days. The laypress is basically damning Celebrex and Bextra on one or two negative study outcomes, which compared to the entire database of info on these drugs are true anomalies. From a biochemical viewpoint, though they are in the same class, Vioxx and Celebrex are starkly different in molecular structure. Celebrex and Bextra contain a sulfonamide chain. This chain is responsible for the rare but serious skin reactions both these drugs can cause (of course a list of forty plus drugs currently on the market carry greater risk of producing this skin reaction, but you don't ever hear about that). This chemical chain also has a far different effect on both platelets and the walls of blood vessels. Basically Celebrex and Bextra make platelets less sticky and the blood vessel walls more pliable and flexible. Vioxx, on the other hand, makes platelets more sticky and increases sheer stress on the walls of blood vessels, making a heart attack far more likely to occur. As for some of the critics, Eric Topol of the Cleveland Clinic, advises several hedge funds (most likely why he will not be part of the new study looking at Cele brex, Aleve, and Motrin in osteoarthritis patients for increased CV risk). Garret Fitzgerald, who argues about a COX2 class effect does so citing 3 sources of information, 2 of which are his own papers (not studies, opinion papers), and data from a COX2 that has yet to even be approved. He was also denied research money by both Pfizer and Merck in the past (score to settle, perhaps?). I just wish all these people would leave the science to scientists. Their grossly uninformed and unscientific statements do nothing more than create pandemonium and scare people into swallowing handfuls of aspirin and tylenol, both far more dangerous pharmacotherapies than Celebrex.